Inorganic salts of sulfurous acid have heretofore been discovered by one of us (Jose Antonio Arias Alvarez) to have anticoagulant and antithrombotic properties; see U.S. Ser. No. 164,845, filed June 30, 1980, now abandoned, refiled as U.S. Ser. No. 227,382, filed Jan. 22, 1981, now abandoned, refiled as U.S. Ser. No. 271,850 filed June 16, 1981, now abandoned, and refiled as U.S. Ser. No. 337,176 on Jan. 5, 1982.
So far as is now known, lower alkyl amine sulfite and bisulfite compounds have never previously been used as anticoagulant and/or antithrombotic agents.
Anticoagulants and antithrombotics are a group of compounds with diversified pharmacologic actions, used in a variety of chemical thrombotic disorders. Thrombotic disorders are generally divided into venous thrombosis and arterial occulsive disorders. Venous thrombosis of the lower extremities is important because it can cause pulmonary embolisms which may be fatal. Heparin and warfarin are commonly used in clinical medicine for prevention and treatment of deep venous thrombosis and pulmonary embolism. Their pharmacological actions are in the inhibition of blood coagulation activity (i.e., heparin) or of synthesis of coagulation factors (i.e., warfarin). Platelets play an important part in arterial thrombosis. Drugs that inhibit platelet aggregation are generally regarded as being potentially useful for prophylactic therapy of arterial thrombotic disorders, including, for example, stroke, myocardial infarction, and peripheral vascular disease. Despite the availability of many agents that possess anti-platelet aggregating properties, only few are currently under clinical trials (i.e., aspirin, dipyridamole, sulfinpyrazone). None of these exhibit unequivocal efficacy. Compounds with specific pharmacological action are urgently sought in order to provide better medical care for patients with these serious disorders.
An anticoagulant agent is a substance which inhibits coagulation of the blood.
An anti-platelet aggregating agent is a substance which inhibits platelet aggregation.
An antithrombotic agent is a substance which inhibits formation or development of a thrombus (or thrombosis). For present patent purposes, it will be understood that the term "thrombus" or equivalent includes the subject matter of the term "embolus" unless otherwise specifically indicated. In general, an antithrombotic agent may display in the presence of mammalian blood or appropriately prepared plasma anticoagulant activity and/or anti-platelet aggregating activity.